“TAD cliques shape the 4-dimensional genome during terminal differentiation”
Tuesday July 2nd, 12:15, Genopode, auditorium A
Genomic information is selectively used to direct spatial and temporal gene expression during differentiation. Interactions between topologically associated domains (TADs) and between chromatin and the nuclear lamina organize and position chromosomes in the nucleus. However, how these genomic organizers together shape genome architecture is unclear. Using a dual-lineage differentiation system, we report here long-range TAD-TAD interactions forming dynamic constitutive and variable TAD cliques. A differentiation-coupled relationship between TAD cliques and lamina-associated domains suggests that TAD cliques stabilize heterochromatin at the nuclear periphery. We also provide evidence of dynamic TAD cliques during mouse embryonic stem cell differentiation and somatic cell reprogramming, and of inter-TAD associations in single-cell Hi-C data. TAD cliques represent a new level of 4-dimensional genome conformation reinforcing the silencing of repressed developmental genes.